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[PMID]:29310349
[Au] Autor:Hong Y; Hao Y; Hu J; Xu B; Shan H; Wang X
[Ad] Endereço:Department of Urology.
[Ti] Título:Adrenocortical oncocytoma: 11 Case reports and review of the literature.
[So] Source:Medicine (Baltimore);96(48):e8750, 2017 Dec.
[Is] ISSN:1536-5964
[Cp] País de publicação:United States
[La] Idioma:eng
[Ab] Resumo:RATIONALE: Adrenocortical oncocytoma is an extremely rare tumor of the adrenal gland. Its diagnostic criteria and biological behavior has not yet reached a consensus. The purpose of this study is to investigate the clinical characteristics of adrenocortical oncocytoma. PATIENT CONCERNS: The clinical data from 11 cases of adrenocortical oncocytoma were retrospectively analyzed. Five patients found the tumor incidentally during the healthy examination, and 3 cases found the tumor during the diagnostic work-up for the evaluation of flank pain or hypertension. A female patient manifested virilization, and Cushing's syndrome showed in two patients. The tumor diameter was ranging from 2.0-13.0 cm. DIAGNOSES: The serum cortisol, plasma aldosterone and catecholamine metabolites were used to evaluate the function of the tumors, and enhanced CT scan was used to confirm the tumor boundary, enhancement, and lymph nodes condition. INTERVENTIONS: Seven cases underwent laparoscopic adrenal tumor resection, 4 patients underwent open surgery. Pathological report indicated adrenocortical oncocytoma in all cases, three of which were potentially malignant. OUTCOMES: The patients were followed up for 19-72 months, no local recurrence and distant metastases were detected in 3 cases of malignant potential cases. LESSONS: The majority of adrenocortical oncocytoma with or without function are benign, and close follow-up observation is essential.
[Mh] Termos MeSH primário: Adenoma Oxífilo/patologia
Neoplasias do Córtex Suprarrenal/patologia
[Mh] Termos MeSH secundário: Adulto
Biomarcadores Tumorais/sangue
Pré-Escolar
Feminino
Seres Humanos
Achados Incidentais
Masculino
Meia-Idade
Estudos Retrospectivos
Tomografia Computadorizada por Raios X
[Pt] Tipo de publicação:CASE REPORTS; JOURNAL ARTICLE; REVIEW
[Nm] Nome de substância:
0 (Biomarkers, Tumor)
[Em] Mês de entrada:1801
[Cu] Atualização por classe:180115
[Lr] Data última revisão:
180115
[Sb] Subgrupo de revista:AIM; IM
[Da] Data de entrada para processamento:180110
[St] Status:MEDLINE
[do] DOI:10.1097/MD.0000000000008750


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[PMID]:29187510
[Au] Autor:Laufs V; Altieri B; Sbiera S; Kircher S; Steinhauer S; Beuschlein F; Quinkler M; Willenberg HS; Rosenwald A; Fassnacht M; Ronchi CL
[Ad] Endereço:Division of Endocrinology and DiabetesDepartment of Internal Medicine I, University Hospital, University of Wuerzburg, Wuerzburg, Germany.
[Ti] Título:ERCC1 as predictive biomarker to platinum-based chemotherapy in adrenocortical carcinomas.
[So] Source:Eur J Endocrinol;178(2):183-190, 2018 Feb.
[Is] ISSN:1479-683X
[Cp] País de publicação:England
[La] Idioma:eng
[Ab] Resumo:OBJECTIVE: Platinum-based chemotherapy (PBC) is the most effective cytotoxic treatment for advanced adrenocortical carcinoma (ACC). Excision repair cross complementing group 1 (ERCC1) plays a critical role in the repair of platinum-induced DNA damage. Two studies investigating the role of ERCC1 immunostaining as a predictive marker for the response to PBC in ACC had reported conflicting results. Both studies used the ERCC1-antibody clone 8F1 that later turned out to be not specific. The aim of this study was to evaluate the predictive role of ERCC1 with a new specific antibody in a larger series of ACC. DESIGN AND METHODS: 146 ACC patients with available FFPE slides were investigated. All patients underwent PBC (median cycles = 6), including cisplatin ( = 131) or carboplatin ( = 15), in most cases combined with etoposide ( = 144), doxorubicin ( = 131) and mitotane ( = 131). Immunostaining was performed with the novel ERCC1-antibody clone 4F9. The relationship between ERCC1 expression and clinicopathological parameters, as well as best objective response to therapy and progression-free survival (PFS) during PBC was evaluated. RESULTS: High ERCC1 expression was observed in 66% of ACC samples. During PBC, 43 patients experienced objective response (29.5%), 49 stable disease (33.6%), 8 mixed response (5.5%) and 46 progressive disease (31.5%) without any relationship with the ERCC1 immunostaining. No significant correlation was also found between ERCC1 expression and progression-free survival (median 6.5 vs 6 months, , HR = 1.23, 95% CI = 0.82-2.0). CONCLUSION: ERCC1 expression is not directly associated with sensitivity to PBC in ACC. Thus, other predictive biomarkers are required to support treatment decisions in patients with ACC.
[Mh] Termos MeSH primário: Neoplasias do Córtex Suprarrenal/tratamento farmacológico
Carcinoma Adrenocortical/tratamento farmacológico
Biomarcadores Tumorais/análise
Carboplatina/uso terapêutico
Cisplatino/uso terapêutico
Proteínas de Ligação a DNA/análise
Endonucleases/análise
[Mh] Termos MeSH secundário: Neoplasias do Córtex Suprarrenal/química
Carcinoma Adrenocortical/química
Adulto
Idoso
Protocolos de Quimioterapia Combinada Antineoplásica/uso terapêutico
Intervalo Livre de Doença
Feminino
Seres Humanos
Imuno-Histoquímica
Masculino
Meia-Idade
Resultado do Tratamento
[Pt] Tipo de publicação:JOURNAL ARTICLE
[Nm] Nome de substância:
0 (Biomarkers, Tumor); 0 (DNA-Binding Proteins); BG3F62OND5 (Carboplatin); EC 3.1.- (ERCC1 protein, human); EC 3.1.- (Endonucleases); Q20Q21Q62J (Cisplatin)
[Em] Mês de entrada:1801
[Cu] Atualização por classe:180110
[Lr] Data última revisão:
180110
[Sb] Subgrupo de revista:IM
[Da] Data de entrada para processamento:171201
[St] Status:MEDLINE
[do] DOI:10.1530/EJE-17-0788


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[PMID]:29283337
[Au] Autor:Ertan Y; Argon A; Özdemir M; Yürekli BPS; Dökümcü Z; Makay Ö
[Ad] Endereço:Department of Pathology, Ege University, Izmir, Turkey.
[Ti] Título:Oncocytic Adreno Cortical Tumors: Pathological Features of 16 Cases and Review of the Literature.
[So] Source:J Environ Pathol Toxicol Oncol;36(3):237-244, 2017.
[Is] ISSN:2162-6537
[Cp] País de publicação:United States
[La] Idioma:eng
[Ab] Resumo:Oncocytic neoplasms of the adrenal gland are extremely rare tumors. These tumors differ from their nononcocytic counterparts in some respects. The aim of this study was to review and discuss the clinical, histological, and immunohistochemical features of as well as the prognosis for these rare tumors. In total, 16 cases diagnosed as adrenocortical oncocytic neoplasms between January 2011 and December 2016 were included in the study. The demographic data, gross characteristics, histological data, and immunohistochemical data (Chromogranin-A, Synaptophysin, α-Inhibin, Melan-A, Ki67, PHH3) were reevaluated. The follow-up data for these patients were added in January 2017. Of the 16 cases, 12 were adrenocortical adenoma, 1 was borderline adrenocortical tumor, and 3 were adrenocortical carcinoma. The tumors equally affected both genders. The tumors were not generally large. Tumor cells had pleomorphic nuclei in ten cases, but it was more obvious in one case. The mitotic figure count was low in most tumors. Atypical mitosis and necrosis were observed in three and four tumors, respectively. None of cases included sinusoidal invasion, vascular invasion, or capsular invasion. We detected the expression of at least one specific marker (e.g., Melan-A, Inhibin-α) of the adrenal cortex in all tumors. None of the tumors were immunoreactive for Chromogranin-A. Ki-67 proliferation index was lower than 5% in all cases except three oncocytic carcinomas. In two cases, PHH3 positivity was not seen, while it was lower than 3 of 10 high-powered fields in ten cases and higher in 4 cases. All patients were alive and disease free except for two patients with adrenocortical carcinoma. In conclusion, determining the clinical, histological, and immunohistochemical characteristics of these extremely rare tumors can provide important information for early diagnosis, treatment, and follow-up of these cases.
[Mh] Termos MeSH primário: Neoplasias do Córtex Suprarrenal/patologia
[Mh] Termos MeSH secundário: Adolescente
Neoplasias do Córtex Suprarrenal/química
Adulto
Criança
Pré-Escolar
Cromogranina A/análise
Feminino
Seres Humanos
Imuno-Histoquímica
Lactente
Recém-Nascido
Antígeno Ki-67/análise
Masculino
Meia-Idade
Estudos Retrospectivos
Adulto Jovem
[Pt] Tipo de publicação:JOURNAL ARTICLE; REVIEW
[Nm] Nome de substância:
0 (Chromogranin A); 0 (Ki-67 Antigen)
[Em] Mês de entrada:1801
[Cu] Atualização por classe:180104
[Lr] Data última revisão:
180104
[Sb] Subgrupo de revista:IM
[Da] Data de entrada para processamento:171229
[St] Status:MEDLINE
[do] DOI:10.1615/JEnvironPatholToxicolOncol.2017021895


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[PMID]:27770290
[Au] Autor:Lee CW; Salem AI; Schneider DF; Leverson GE; Tran TB; Poultsides GA; Postlewait LM; Maithel SK; Wang TS; Hatzaras I; Shenoy R; Phay JE; Shirley L; Fields RC; Jin LX; Pawlik TM; Prescott JD; Sicklick JK; Gad S; Yopp AC; Mansour JC; Duh QY; Seiser N; Solorzano CC; Kiernan CM; Votanopoulos KI; Levine EA; Weber SM
[Ad] Endereço:Department of Surgery, University of Wisconsin School of Medicine and Public Health, H4/730 Clinical Science Center, Madison, WI, 53792, USA.
[Ti] Título:Minimally Invasive Resection of Adrenocortical Carcinoma: a Multi-Institutional Study of 201 Patients.
[So] Source:J Gastrointest Surg;21(2):352-362, 2017 02.
[Is] ISSN:1873-4626
[Cp] País de publicação:United States
[La] Idioma:eng
[Ab] Resumo:BACKGROUND AND OBJECTIVES: Minimally invasive surgery for adrenocortical carcinoma (ACC) is controversial. We sought to evaluate the perioperative and long-term outcomes following minimally invasive (MIS) and open resection (OA) of ACC in patients treated with curative intent surgery. METHODS: Retrospective data from patients who underwent adrenalectomy for primary ACC at 13 tertiary care cancer centers were analyzed, including demographics, clinicopathological, and operative outcomes. Outcomes following MIS were compared to OA. RESULTS: A total of 201 patients were evaluated including 47 MIS and 154 OA. There was no difference in utilization of MIS approach among institutions (p = 0.24) or 30-day morbidity (29.3 %, MIS, vs. 30.9 %, OA; p = 0.839). The only preoperatively determined predictor for MIS was smaller tumor size (p < 0.001). There was no difference in rates of intraoperative tumor rupture (p = 0.612) or R0 resection (p = 0.953). Only EBL (p = 0.038) and T stage (p = 0.045) were independent prognostic indicators of overall survival after adjusting for significant factors. The surgical approach was not associated with overall or disease-free survival. CONCLUSION: MIS adrenalectomy may be utilized for preoperatively determined ACC ≤ 10.0 cm; however, OA should be utilized for adrenal masses with either preoperative or intraoperative evidence of local invasion or enlarged lymph nodes, regardless of size.
[Mh] Termos MeSH primário: Neoplasias do Córtex Suprarrenal/cirurgia
Adrenalectomia
Carcinoma Adrenocortical/cirurgia
Procedimentos Cirúrgicos Minimamente Invasivos
[Mh] Termos MeSH secundário: Neoplasias do Córtex Suprarrenal/mortalidade
Neoplasias do Córtex Suprarrenal/patologia
Carcinoma Adrenocortical/mortalidade
Carcinoma Adrenocortical/patologia
Adulto
Idoso
Idoso de 80 Anos ou mais
Intervalo Livre de Doença
Feminino
Seres Humanos
Masculino
Meia-Idade
Prognóstico
Estudos Retrospectivos
Taxa de Sobrevida
Adulto Jovem
[Pt] Tipo de publicação:JOURNAL ARTICLE; MULTICENTER STUDY
[Em] Mês de entrada:1712
[Cu] Atualização por classe:180102
[Lr] Data última revisão:
180102
[Sb] Subgrupo de revista:IM
[Da] Data de entrada para processamento:161023
[St] Status:MEDLINE
[do] DOI:10.1007/s11605-016-3262-4


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[PMID]:28973495
[Au] Autor:Creemers SG; Korpershoek E; Atmodimedjo PN; Dinjens WNM; van Koetsveld PM; Feelders RA; Hofland LJ
[Ad] Endereço:Division of Endocrinology, Department of Internal Medicine, Erasmus Medical Center, University Medical Center Rotterdam, Rotterdam 3000 CA, The Netherlands.
[Ti] Título:Identification of Mutations in Cell-Free Circulating Tumor DNA in Adrenocortical Carcinoma: A Case Series.
[So] Source:J Clin Endocrinol Metab;102(10):3611-3615, 2017 Oct 01.
[Is] ISSN:1945-7197
[Cp] País de publicação:United States
[La] Idioma:eng
[Ab] Resumo:Context: The disease course of adrenocortical carcinoma (ACC) patients is heterogeneous. A marker for prognosis and treatment response would facilitate choices for diagnosis and therapy. In other cancer types, circulating cell-free tumor DNA predicted tumor dynamics. Case Descriptions: The present pilot study included six patients. Next-generation sequencing (NGS) showed mutations in three ACC cases. From these patients, blood was drawn before (1 to 2 weeks) and after surgery and cell-free circulating DNA (cfDNA) was isolated. Tumor-specific mutations were found in the cfDNA of one of the three patients, with metastasized ACC at diagnosis. NGS of the tumor showed an NRAS mutation (c.182A>G:p.Q61R) in 78%, a TP53 mutation (c.856G>A:p.E286K) in 60%, and a TERT gene mutation (1295250C>T) in 28% of the reads. The preoperative cfDNA showed the same mutations at a frequency of 64%, 32%, and 2%, respectively. The postoperative cfDNA showed the same mutations but at lower frequencies (52%, 16%, and 3%, respectively). The patient was postoperatively treated with mitotane and chemotherapy. No mutations were detected in the corresponding leukocyte DNA or in the cfDNA from the two other patients. Conclusions: To the best of our knowledge, we report for the first time mutations occurring at high levels in cfDNA collected before and after surgery from one of three patients, after previous identification in the tumor. However, in the cfDNA from two patients with known mutations, we were unable to reliably detect mutations in the cfDNA. Our results indicate that mutation detection in cfDNA can vary among ACC patients, and other approaches might be required to detect the tumor response and monitor progressive disease.
[Mh] Termos MeSH primário: Neoplasias do Córtex Suprarrenal/genética
Carcinoma Adrenocortical/genética
DNA de Neoplasias/análise
Células Neoplásicas Circulantes/metabolismo
[Mh] Termos MeSH secundário: Neoplasias do Córtex Suprarrenal/patologia
Carcinoma Adrenocortical/patologia
Idoso
Análise Mutacional de DNA/métodos
DNA de Neoplasias/metabolismo
Feminino
GTP Fosfo-Hidrolases/genética
Genes p53
Sequenciamento de Nucleotídeos em Larga Escala
Seres Humanos
Masculino
Proteínas de Membrana/genética
Meia-Idade
Mutação de Sentido Incorreto
Células Neoplásicas Circulantes/patologia
Projetos Piloto
Telomerase/genética
beta Catenina/genética
[Pt] Tipo de publicação:CASE REPORTS; JOURNAL ARTICLE
[Nm] Nome de substância:
0 (CTNNB1 protein, human); 0 (DNA, Neoplasm); 0 (Membrane Proteins); 0 (beta Catenin); EC 2.7.7.49 (TERT protein, human); EC 2.7.7.49 (Telomerase); EC 3.6.1.- (GTP Phosphohydrolases); EC 3.6.1.- (NRAS protein, human)
[Em] Mês de entrada:1710
[Cu] Atualização por classe:171031
[Lr] Data última revisão:
171031
[Sb] Subgrupo de revista:AIM; IM
[Da] Data de entrada para processamento:171004
[St] Status:MEDLINE
[do] DOI:10.1210/jc.2017-00174


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[PMID]:28911143
[Au] Autor:Sbiera S; Sbiera I; Ruggiero C; Doghman-Bouguerra M; Korpershoek E; de Krijger RR; Ettaieb H; Haak H; Volante M; Papotti M; Reimondo G; Terzolo M; Luconi M; Nesi G; Mannelli M; Libé R; Ragazzon B; Assié G; Bertherat J; Altieri B; Fadda G; Rogowski-Lehmann N; Reincke M; Beuschlein F; Fassnacht M; Lalli E
[Ad] Endereço:Department of Internal Medicine I - Division of Endocrinology and Diabetes, University Hospital, University of Würzburg, 97080 Wurzburg, Germany.
[Ti] Título:Assessment of VAV2 Expression Refines Prognostic Prediction in Adrenocortical Carcinoma.
[So] Source:J Clin Endocrinol Metab;102(9):3491-3498, 2017 Sep 01.
[Is] ISSN:1945-7197
[Cp] País de publicação:United States
[La] Idioma:eng
[Ab] Resumo:Context: Adrenocortical carcinoma (ACC) is a rare endocrine malignancy with overall poor prognosis. The Ki67 labeling index (LI) has a major prognostic role in localized ACC after complete resection, but its estimates may suffer from considerable intra- and interobserver variability. VAV2 overexpression induced by increased Steroidogenic Factor-1 dosage is an essential factor driving ACC tumor cell invasion. Objective: To assess the prognostic role of VAV2 expression in ACC by investigation of a large cohort of patients. Design, Setting, and Participants: A total of 171 ACC cases (157 primary tumors, six local recurrences, eight metastases) from seven European Network for the Study of Adrenal Tumors centers were studied. Outcome Measurements: H-scores were generated to quantify VAV2 expression. VAV2 expression was divided into two categories: low (H-score, <2) and high (H-score, ≥2). The Ki67 LI retrieved from patients' pathology records was also categorized into low (<20%) and high (≥20%). Clinical and immunohistochemical markers were correlated with progression-free survival (PFS) and overall survival (OS). Results: VAV2 expression and Ki67 LI were significantly correlated with each other and with PFS and OS. Heterogeneity of VAV2 expression inside the same tumor was very low. Combined assessment of VAV2 expression and Ki67 LI improved patient stratification to low-risk and high-risk groups. Conclusion: Combined assessment of Ki67 LI and VAV2 expression improves prognostic prediction in ACC.
[Mh] Termos MeSH primário: Neoplasias do Córtex Suprarrenal/sangue
Neoplasias do Córtex Suprarrenal/mortalidade
Carcinoma Adrenocortical/sangue
Carcinoma Adrenocortical/mortalidade
Biomarcadores Tumorais/sangue
Proteínas Proto-Oncogênicas c-vav/metabolismo
[Mh] Termos MeSH secundário: Neoplasias do Córtex Suprarrenal/terapia
Carcinoma Adrenocortical/terapia
Adulto
Idoso
Análise de Variância
Biópsia por Agulha
Estudos de Coortes
Terapia Combinada
Intervalo Livre de Doença
Europa (Continente)
Feminino
Seres Humanos
Imuno-Histoquímica
Internacionalidade
Estimativa de Kaplan-Meier
Masculino
Meia-Idade
Análise Multivariada
Recidiva Local de Neoplasia/mortalidade
Recidiva Local de Neoplasia/patologia
Valor Preditivo dos Testes
Prognóstico
Proteínas Proto-Oncogênicas c-vav/sangue
Análise de Sobrevida
Resultado do Tratamento
[Pt] Tipo de publicação:JOURNAL ARTICLE; MULTICENTER STUDY
[Nm] Nome de substância:
0 (Biomarkers, Tumor); 0 (Proto-Oncogene Proteins c-vav); 0 (VAV2 protein, human)
[Em] Mês de entrada:1710
[Cu] Atualização por classe:171012
[Lr] Data última revisão:
171012
[Sb] Subgrupo de revista:AIM; IM
[Da] Data de entrada para processamento:170916
[St] Status:MEDLINE
[do] DOI:10.1210/jc.2017-00984


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[PMID]:28826686
[Au] Autor:Peverelli E; Catalano R; Giardino E; Treppiedi D; Morelli V; Ronchi CL; Vaczlavik A; Fusco N; Ferrero S; Bertherat J; Beuschlein F; Chiodini I; Arosio M; Spada A; Mantovani G
[Ad] Endereço:Endocrine Unit, Fondazione IRCCS Ca' Granda Ospedale Maggiore Policlinico, Milan, Italy; Department of Clinical Sciences and Community Health, University of Milan, Milan, Italy. Electronic address: erika.peverelli@guest.unimi.it.
[Ti] Título:Cofilin is a cAMP effector in mediating actin cytoskeleton reorganization and steroidogenesis in mouse and human adrenocortical tumor cells.
[So] Source:Cancer Lett;406:54-63, 2017 Oct 10.
[Is] ISSN:1872-7980
[Cp] País de publicação:Ireland
[La] Idioma:eng
[Ab] Resumo:cAMP pathway plays a major role in the pathogenesis of cortisol-producing adrenocortical adenomas (CPA). cAMP-induced steroidogenesis is preceded by actin cytoskeleton reorganization, a process regulated by cofilin activity. In this study we investigated cofilin role in mediating cAMP effects on cell morphology and steroidogenesis in adrenocortical tumor cells. We demonstrated that forskolin induced cell rounding and strongly reduced phosphorylated (P)-cofilin/total cofilin ratio in Y1 (-52 ± 16%, p < 0.001) and human CPA cells (-53 ± 18%, p < 0.05). Cofilin silencing significantly reduced both forskolin-induced morphological changes and progesterone production (1.3-fold vs 1.8-fold in controls, p < 0.05), whereas transfection of wild-type or S3A (active), but not S3D (inactive) cofilin, potentiated forskolin effects on cell rounding and increased 3-fold progesterone synthesis with respect to control (p < 0.05). Furthermore, cofilin dephosphorylation by a ROCK inhibitor potentiated forskolin-induced cell rounding and steroidogenesis (2-fold increase vs forskolin alone). Finally, we found a reduced P-cofilin/total cofilin ratio and increased cofilin expression in CPA vs endocrine inactive adenomas by western blot and immunohistochemistry. Overall, these results identified cofilin as a mediator of cAMP effects on both morphological changes and steroidogenesis in mouse and human adrenocortical tumor cells.
[Mh] Termos MeSH primário: Citoesqueleto de Actina/metabolismo
Fatores de Despolimerização de Actina/metabolismo
Neoplasias do Córtex Suprarrenal/metabolismo
Adenoma Adrenocortical/metabolismo
AMP Cíclico/farmacologia
Esteroides/biossíntese
[Mh] Termos MeSH secundário: Fatores de Despolimerização de Actina/antagonistas & inibidores
Fatores de Despolimerização de Actina/genética
Neoplasias do Córtex Suprarrenal/tratamento farmacológico
Neoplasias do Córtex Suprarrenal/patologia
Adenoma Adrenocortical/tratamento farmacológico
Adenoma Adrenocortical/patologia
Animais
Colforsina/farmacologia
Seres Humanos
Hidrocortisona/metabolismo
Camundongos
Fosforilação/efeitos dos fármacos
RNA Interferente Pequeno/genética
Células Tumorais Cultivadas
Vasodilatadores/farmacologia
[Pt] Tipo de publicação:JOURNAL ARTICLE
[Nm] Nome de substância:
0 (Actin Depolymerizing Factors); 0 (RNA, Small Interfering); 0 (Steroids); 0 (Vasodilator Agents); 1F7A44V6OU (Colforsin); E0399OZS9N (Cyclic AMP); WI4X0X7BPJ (Hydrocortisone)
[Em] Mês de entrada:1709
[Cu] Atualização por classe:170921
[Lr] Data última revisão:
170921
[Sb] Subgrupo de revista:IM
[Da] Data de entrada para processamento:170823
[St] Status:MEDLINE


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[PMID]:28819017
[Au] Autor:Else T; Lerario AM; Everett J; Haymon L; Wham D; Mullane M; Wilson TL; Rainville I; Rana H; Worth AJ; Snyder NW; Blair IA; McKay R; Kilbridge K; Hammer G; Barletta J; Vaidya A
[Ad] Endereço:Division of MetabolismEndocrinology and Diabetes, Department of Internal Medicine, University of Michigan, Ann Arbor, Michigan, USA telse@umich.med.edu anandvaidya@bwh.harvard.edu.
[Ti] Título:Adrenocortical carcinoma and succinate dehydrogenase gene mutations: an observational case series.
[So] Source:Eur J Endocrinol;177(5):439-444, 2017 Nov.
[Is] ISSN:1479-683X
[Cp] País de publicação:England
[La] Idioma:eng
[Ab] Resumo:OBJECTIVE: Germline loss-of-function mutations in succinate dehydrogenase ( ) genes results in rare tumor syndromes that include pheochromocytoma, paraganglioma, and others. Here we report a case series of patients with adrenocortical carcinoma (ACC) that harbor mutations. PATIENTS AND RESULTS: We report four unrelated patients with ACC and mutations. All cases presented with Cushing syndrome and large adrenal masses that were confirmed to be ACC on pathology. All four ACC specimens were found to have truncating mutations in either or , while cases 1, 2 and 3 also had the mutations confirmed in the germline: Case 1: c.397C > T, pR133X; Case 2: c.43C > T, p.R15X; Case 3: c.91C > T, p.R31X; Case 4: c.1258C > T, p.Q420X. Notably, Case 1 had a father and daughter who both harbored the same germline mutation, and the father had a paraganglioma and renal cell carcinoma. A combination of next generation sequencing, and/or immunohistochemistry, and/or mass spectroscopy was used to determine whether there was loss of heterozygosity and/or loss of SDH protein expression or function within the ACC. Potential evidence of loss of heterozygosity was observed only in Case 2. CONCLUSIONS: We observed truncating mutations in or in the ACC and/or germline of four unrelated patients. Given how statistically improbable the concurrence of ACC and pathogenic germline mutations is expected to be, these observations raise the question whether ACC may be a rare manifestation of mutation syndromes. Further studies are needed to investigate the possible role of SDH deficiency in ACC pathogenesis.
[Mh] Termos MeSH primário: Neoplasias do Córtex Suprarrenal/diagnóstico
Neoplasias do Córtex Suprarrenal/genética
Carcinoma Adrenocortical/diagnóstico
Carcinoma Adrenocortical/genética
Mutação/genética
Succinato Desidrogenase/genética
[Mh] Termos MeSH secundário: Adulto
Feminino
Seres Humanos
Masculino
Linhagem
Adulto Jovem
[Pt] Tipo de publicação:CASE REPORTS; JOURNAL ARTICLE; OBSERVATIONAL STUDY
[Nm] Nome de substância:
0 (SDHD protein, human); EC 1.3.99.1 (Succinate Dehydrogenase)
[Em] Mês de entrada:1710
[Cu] Atualização por classe:171012
[Lr] Data última revisão:
171012
[Sb] Subgrupo de revista:IM
[Da] Data de entrada para processamento:170819
[St] Status:MEDLINE
[do] DOI:10.1530/EJE-17-0358


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[PMID]:28780517
[Au] Autor:Reimondo G; Puglisi S; Zaggia B; Basile V; Saba L; Perotti P; De Francia S; Volante M; Zatelli MC; Cannavò S; Terzolo M
[Ad] Endereço:Internal Medicine 1Department of Clinical and Biological Sciences, University of Turin, Orbassano, Italy.
[Ti] Título:Effects of mitotane on the hypothalamic-pituitary-adrenal axis in patients with adrenocortical carcinoma.
[So] Source:Eur J Endocrinol;177(4):361-367, 2017 Oct.
[Is] ISSN:1479-683X
[Cp] País de publicação:England
[La] Idioma:eng
[Ab] Resumo:OBJECTIVE: Mitotane, a drug used to treat adrenocortical cancer (ACC), inhibits multiple enzymatic steps of adrenocortical steroid biosynthesis, potentially causing adrenal insufficiency. Recent studies have also documented a direct inhibitory effect of mitotane at the pituitary level. The present study was aimed to assess the hypothalamic-pituitary-adrenal axis in patients with ACC receiving mitotane. DESIGN AND METHODS: We prospectively enrolled 16 patients on adjuvant treatment with mitotane after radical surgical resection of ACC, who underwent standard hormone evaluation and h-CRH stimulation. A group of 10 patients with primary adrenal insufficiency (PAI) served as controls for the CRH test. RESULTS: We demonstrated a close correlation between cortisol-binding globulin (CBG) and plasma mitotane levels, and a non-significant trend between mitotane dose and either serum or salivary cortisol in ACC patients. We did not find any correlation between the dose of cortisone acetate and either ACTH or cortisol levels. ACTH levels were significantly higher in patients with PAI than that in patients with ACC, both in baseline conditions (88.99 (11.04-275.00) vs 24.53 (6.16-121.88) pmol/L, = 0.031) and following CRH (158.40 (34.32-275.00) vs 67.43 (8.8-179.52) pmol/L = 0.016). CONCLUSIONS: The observation of lower ACTH levels in patients with ACC than that in patients with PAI, both in basal conditions and after CRH stimulation, suggests that mitotane may play an inhibitory effect on ACTH secretion at the pituitary levels. In conclusion, the present study shows that mitotane affects the HPA axis at multiple levels and no single biomarker may be used for the assessment of adrenal insufficiency.
[Mh] Termos MeSH primário: Neoplasias do Córtex Suprarrenal/tratamento farmacológico
Carcinoma Adrenocortical/tratamento farmacológico
Antineoplásicos Hormonais/uso terapêutico
Sistema Hipotálamo-Hipofisário/efeitos dos fármacos
Mitotano/uso terapêutico
Sistema Hipófise-Suprarrenal/efeitos dos fármacos
[Mh] Termos MeSH secundário: Neoplasias do Córtex Suprarrenal/sangue
Carcinoma Adrenocortical/sangue
Hormônio Adrenocorticotrópico/sangue
Adulto
Idoso
Antineoplásicos Hormonais/sangue
Antineoplásicos Hormonais/farmacologia
Feminino
Seres Humanos
Sistema Hipotálamo-Hipofisário/metabolismo
Masculino
Meia-Idade
Mitotano/sangue
Mitotano/farmacologia
Sistema Hipófise-Suprarrenal/metabolismo
Estudos Prospectivos
Resultado do Tratamento
[Pt] Tipo de publicação:JOURNAL ARTICLE
[Nm] Nome de substância:
0 (Antineoplastic Agents, Hormonal); 78E4J5IB5J (Mitotane); 9002-60-2 (Adrenocorticotropic Hormone)
[Em] Mês de entrada:1710
[Cu] Atualização por classe:171003
[Lr] Data última revisão:
171003
[Sb] Subgrupo de revista:IM
[Da] Data de entrada para processamento:170807
[St] Status:MEDLINE
[do] DOI:10.1530/EJE-17-0452


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[PMID]:28738949
[Au] Autor:Poorman CE; Postlewait LM; Ethun CG; Tran TB; Prescott JD; Pawlik TM; Wang TS; Glenn J; Hatzaras I; Shenoy R; Phay JE; Keplinger K; Fields RC; Jin LX; Weber SM; Salem A; Sicklick JK; Gad S; Yopp AC; Mansour JC; Duh QY; Seiser N; Solorzano CC; Kiernan CM; Votanopoulos KI; Levine EA; Staley CA; Poultsides GA; Maithel SK
[Ti] Título:Blood Transfusion and Survival for Resected Adrenocortical Carcinoma: A Study from the United States Adrenocortical Carcinoma Group.
[So] Source:Am Surg;83(7):761-768, 2017 Jul 01.
[Is] ISSN:1555-9823
[Cp] País de publicação:United States
[La] Idioma:eng
[Ab] Resumo:Perioperative blood transfusion is associated with decreased survival in pancreatic, gastric, and liver cancer. The effect of transfusion in adrenocortical carcinoma (ACC) has not been studied. Patients with available transfusion data undergoing curative-intent resection of ACC from 1993 to 2014 at 13 institutions comprising the United States Adrenocortical Carcinoma Group were included. Factors associated with blood transfusion were determined. Primary and secondary end points were recurrence-free survival (RFS) and overall survival (OS), respectively. Out of 265 patients, 149 were included for analysis. Out of these, 57 patients (38.3%) received perioperative transfusions. Compared to nontransfused patients, transfused patients more commonly had stage 4 disease (46% vs 24%, P = 0.01), larger tumors (15.8 vs 10.2 cm, P < 0.001), inferior vena cava involvement (24.6% vs 5.4%, P = 0.002), additional organ resection (78.9% vs 36.3%, P < 0.001), and major complications (29% vs 2%, P < 0.001). Transfusion was associated with decreased RFS (8.9 vs 24.7 months, P = 0.006) and OS (22.8 vs 91.0 months, P < 0.001). On univariate Cox regression, transfusion, stage IV, hormonal hypersecretion, and adjuvant therapy were associated with decreased RFS. On multivariable analysis, only transfusion [hazard ratio (HR) = 1.7, 95% confidence interval (CI) =1.0-2.9, P = 0.04], stage IV (HR = 3.2, 95% CI = 1.7-5.9, P < 0.001), and hormonal hypersecretion (HR = 2.6, 95% CI = 1.5-4.2, P < 0.001) were associated with worse RFS. When applying this model to OS, similar associations were seen (transfusion HR = 2.0, 95% CI = 1.1-3.8, P = 0.02; stage 4 HR = 6.2, 95% CI = 3.1-12.4, P < 0.001; hormonal hypersecretion HR = 3.5, 95% CI = 1.9-6.4, P < 0.001). There was no difference in outcomes between patients who received 1 to 2 units versus >2 units of packed red blood cells in median RFS (8.9 vs 8.4 months, P = 0.95) or OS (26.5 vs 18.6 months, P = 0.63). Perioperative transfusion is associated with earlier recurrence and decreased survival after curative-intent resection of ACC. Strategies and protocols to minimize blood transfusion should be developed and followed.
[Mh] Termos MeSH primário: Neoplasias do Córtex Suprarrenal/mortalidade
Neoplasias do Córtex Suprarrenal/cirurgia
Carcinoma Adrenocortical/mortalidade
Carcinoma Adrenocortical/cirurgia
Transfusão de Sangue/estatística & dados numéricos
[Mh] Termos MeSH secundário: Feminino
Seres Humanos
Masculino
Meia-Idade
Prognóstico
Modelos de Riscos Proporcionais
Estudos Retrospectivos
Taxa de Sobrevida
Estados Unidos
[Pt] Tipo de publicação:JOURNAL ARTICLE; MULTICENTER STUDY
[Em] Mês de entrada:1709
[Cu] Atualização por classe:170907
[Lr] Data última revisão:
170907
[Sb] Subgrupo de revista:IM
[Da] Data de entrada para processamento:170726
[St] Status:MEDLINE



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